Semaglutide combined with empagliflozin vs. monotherapy for non-alcoholic fatty liver disease in type 2 diabetes: Study protocol for a randomized clinical trial.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is strongly associated with type 2 diabetes mellitus (T2DM). Lifestyle intervention remains a preferred treatment modality for NAFLD. The glucagon-like peptide (GLP-1) receptor agonists and sodium-glucose cotransporter-2 (SGLT-2) inhibitors have been developed as new glucose-lowering drugs, which can improve fatty liver via an insulin-independent glucose-lowering effect. However, studies exploring the efficacy of GLP-1 receptor agonists combined with SGLT-2 inhibitors in patients with NAFLD and T2DM are scanty. Thus, the present randomised controlled trial aims at comparing the efficacy and safety of semaglutide plus empagliflozin with each treatment alone in patients with NAFLD and T2DM. METHODS: This 52-week double-blinded, randomised, parallel-group, active-controlled trial evaluates the effects of semaglutide, empagliflozin and semaglutide + empagliflozin in 105 eligible overweight/obese subjects with NAFLD and T2DM. The primary outcome will be a change from baseline to week 52 in the controlled attenuation parameter, free fatty acid and glucagon. Secondary endpoints include changes in liver stiffness measurement, liver enzymes, blood glucose, lipid levels, renal function, electrolyte balances, minerals and bone metabolism, cytokines, high-sensitivity C-reactive protein, ferritin, anthropometric indicators, nonalcoholic fatty liver fibrosis score, fibrosis 4 score and homeostatic model assessment for insulin resistance. In addition, intention-to-treat, interim analysis and safety analysis will be performed. DISCUSSION: This double-blinded, randomised, clinical trial involves a multi-disciplinary approach and aims to explore the synergistic effects of the combination of semaglutide and empagliflozin. The results can provide important insights into mechanisms of GLP-1 receptor agonists and/or SGLT-2 inhibitors in patients with NAFLD and T2DM. TRIAL REGISTRATION: This study has been registered with Chinese Clinical Trial Registry (ChiCTR2300070674).

A Predictive Model to Evaluate Pathologic Complete Response in Rectal Adenocarcinoma.

Introduction: Neoadjuvant chemo-radiotherapy (nCRT) before surgery was a standard treatment strategy for locally advanced rectal cancer (LARC). The aim of this study was to assess the relationship between the predictive factors and pathological complete response (pCR) in rectal cancer patients, especially in ultra-low ones. Method: A total of 402 patients were involved in this retrospective study. The logistic regression analyses were used to compare the different subgroups in univariate analysis. Multivariate analysis was performed to determine the independent predictive factors of pCR by using a logistic regression model. Results: A total of 402 patients received preoperative CRT. In all patients, multivariate analysis revealed that circumferential tumor extent rate (CER) (≤ 2/3cycle vs >2/3 cycle, P < .001, OR = 4.834, 95% CI: 2.309-10.121), carcinoembryonic antigen (CEA) level (both ≤ 5 vs pre > 5 and post ≤ 5 vs both > 5, P = .033, OR = 1.537, 95% CI: 1.035-2.281), and interval time between the end of CRT and surgery (P = .031, OR = 2.412, 95% CI: 1.086-5.358) were predictive factors for pCR. The area under the curve (AUC) of the predictive model was 0.709 (95% CI: 0.649-0.769), which was significantly higher than the CER (0.646, 95% CI: 0.584-0.709), interval time (0.563, 95% CI: 0.495-0.631) and CEA level (0.586, 95% CI: 0.518-0.655). In ultra-low rectal patients, multivariate logistic regression analysis revealed that CER (≤ 2/3 cycle vs > 2/3 cycle, P = .003, OR = 7.203, 95% CI: 1.934-26.823) and mismatch repair (MMR) status (pMMR vs dMMR, P = .016, OR = 0.173, 95% CI: 0.041-0.720) were predictive factors for pCR. The AUC of the predictive model was 0.653 (95% CI: 0.474-0.832). Conclusion: New predictive models were varied by the histologic types and MMR statuses to evaluate the trend of tumor response to nCRT in all RC cases and ultra-low RC patients, which may be used to individualize stratify for selected LARC patients.

Quantitative analysis method of Panax notoginseng based on thermal perturbation terahertz two-dimensional correlation spectroscopy.

This paper proposes a Panax notoginseng (P. notoginseng) quantitative analysis based on terahertz time-domain spectroscopy and two-dimensional correlation spectroscopy (2DCOS). By imposing temperature perturbation combined with 2DCOS, the one-dimensional absorbance spectra were transformed into 2DCOS synchronous spectra, which reflected the differences in characteristic information between different P. notoginseng contents more clearly. Then, the feature information of P. notoginseng contents was extracted from the 2DCOS synchronous spectra by a competitive adaptive reweighted sampling (CARS) method and was used to build a quantitative model combined with a support vector regression machine (SVR), called 2DCOS-CARS-SVR. We obtained a more accurate analysis result than the commonly used principal component analysis (PCA)-partial least squares regression (PLSR) and PCA-SVR. The prediction set correlation coefficient and root mean square error reached 0.9915% and 0.8160%, respectively.

Programmed Cell Death in Asthma: Apoptosis, Autophagy, Pyroptosis, Ferroptosis, and Necroptosis.

Bronchial asthma is a complex heterogeneous airway disease, which has emerged as a global health issue. A comprehensive understanding of the different molecular mechanisms of bronchial asthma may be an efficient means to improve its clinical efficacy in the future. Increasing research evidence indicates that some types of programmed cell death (PCD), including apoptosis, autophagy, pyroptosis, ferroptosis, and necroptosis, contributed to asthma pathogenesis, and may become new targets for future asthma treatment. This review briefly discusses the molecular mechanism and signaling pathway of these forms of PCD focuses on summarizing their roles in the pathogenesis and treatment strategies of asthma and offers some efficient means to improve clinical efficacy of therapeutics for asthma in the near future.

Analysis of reaction between vitamin B6 and bovine serum albumin based on a terahertz metamaterial sensor.

A four-peak terahertz metamaterial sensor was used to detect the reaction between different concentrations of vitamin B6 (VB6) and bovine serum albumin (BSA), which achieves a concentration range (0.015-0.125 mg/µl) of VB6 and a maximum binding concentration (0.05 mg/µl) of VB6 and 0.0875 mg/µl BSA. To understand the combination of VB6 and BSA, the reactants between VB (VB1, VB3, and VB5) with the same concentration (0.05 mg/µl) and a BSA solution with a concentration of 0.0875 mg/µl were carried on the surface of the sensor. Experimental results show that the reactants cause the four resonance peaks of the sensor to produce the coincident redshift, which is the same as the order of their binding coefficients determined by the fluorescence method. The experimental process indicates that it is feasible to use terahertz metamaterials to detect the reaction process of organic matter.

7,8-Dihydroxyflavone protects retinal ganglion cells against chronic intermittent hypoxia-induced oxidative stress damage via activation of the BDNF/TrkB signaling pathway.

PURPOSE: Chronic intermittent hypoxia (CIH) plays a key role in the complications of obstructive sleep apnea (OSA), which is strongly associated with retinal and optic nerve diseases. Additionally, the brain-derived neurotrophic factor (BDNF)/tropomyosin receptor kinase B (TrkB) signaling pathway plays an important protective role in neuronal injury. In the present study, we investigated the role of 7,8-dihydroxyflavone (7,8-DHF) in regulating CIH-induced injury in mice retinas and rat primary retinal ganglion cells (RGCs). METHODS: C57BL/6 mice and in vitro primary RGCs were exposed to CIH or normoxia and treated with or without 7,8-DHF. The mice eyeballs or cultured cells were then taken for histochemistry, immunofluorescence or biochemistry, and the protein expression of the BDNF/TrkB signaling pathway analysis. RESULTS: Our results showed that CIH induced oxidative stress (OS) in in vivo and in vitro models and inhibited the conversion of BDNF precursor (pro-BDNF) to a mature form of BDNF, which increased neuronal cell apoptosis. 7,8-DHF reduced the production of reactive oxygen species (ROS) caused by CIH and effectively activated TrkB signals and downstream protein kinase B (Akt) and extracellular signal-regulated kinase (Erk) survival signaling pathways, which upregulated the expression of mature BDNF. ANA-12 (a TrkB specific inhibitor) blocked the protective effect of 7,8-DHF. CONCLUSION: In short, the activation of the BDNF/TrkB signaling pathway alleviated CIH-induced oxidative stress damage of the optic nerve and retinal ganglion cells. 7,8-DHF may serve as a promising agent for OSA related neuropathy.

MicroRNA panel in serum reveals novel diagnostic biomarkers for prostate cancer.

PURPOSE: MicroRNAs (miRNAs), which could be stably preserved and detected in serum or plasma, could act as biomarkers in cancer diagnosis. Prostate cancer is the second cancer in males for incidence. This study aimed to establish a miRNA panel in peripheral serum which could act as a non-invasive biomarker helping diagnosing PC. METHODS: A total of 86 PC patients and 86 normal control serum samples were analyzed through a four-stage experimental process using quantitative real-time polymerase chain reaction. Logistic regression method was used to construct a diagnostic model based on the differentially expressed miRNAs in serum. Receiver operating characteristic curves were constructed to evaluate the diagnostic accuracy. We also compared the 3-miRNA panel with previously reported biomarkers and verified in four public datasets. In addition, the expression characteristics of the identified miRNAs were further explored in tissue and serum exosomes samples. RESULTS: We identified a 3-miRNA signature including up-regulated miR-146a-5p, miR-24-3p and miR-93-5p for PC detection. Areas under the receiver operating characteristic curve of the 3-miRNA panel for the training, testing and external validation phase were 0.819, 0.831 and 0.814, respectively. The identified signature has a very stable diagnostic performance in the large cohorts of four public datasets. Compared with previously identified miRNA biomarkers, the 3-miRNA signature in this study has superior performance in diagnosing PC. What's more, the expression level of miR-93-5p was also elevated in exosomes from PC samples. However, in PC tissues, none of the three miRNAs showed significantly dysregulated expression. CONCLUSIONS: We established a three-miRNA panel (miR-146a-5p, miR-24-3p and miR-93-5p) in peripheral serum which could act as a non-invasive biomarker helping diagnosing PC.

Three plasma-based microRNAs as potent diagnostic biomarkers for endometrial cancer.

BACKGROUND: MicroRNAs (miRNAs), with noticeable stability and unique expression pattern in plasma of patients with various diseases, are powerful non-invasive biomarkers for cancer detection including endometrial cancer (EC). OBJECTIVE: The objective of this study was to identify promising miRNA biomarkers in plasma to assist the clinical screening of EC. METHODS: A total of 93 EC and 79 normal control (NC) plasma samples were analyzed using Quantitative Real-time Polymerase Chain Reaction (qRT-PCR) in this four-stage experiment. The receiver operating characteristic curve (ROC) analysis was conducted to evaluate the diagnostic value. Additionally, the expression features of the identified miRNAs were further explored in tissues and plasma exosomes samples. RESULTS: The expression of miR-142-3p, miR-146a-5p, and miR-151a-5p was significantly overexpressed in the plasma of EC patients compared with NCs. Areas under the ROC curve of the 3-miRNA signature were 0.729, 0.751, and 0.789 for the training, testing, and external validation phases, respectively. The diagnostic performance of the identified signature proved to be stable in the three public datasets and superior to the other miRNA biomarkers in EC diagnosis. Moreover, the expression of miR-151a-5p was significantly elevated in EC plasma exosomes. CONCLUSIONS: A signature consisting of 3 plasma miRNAs was identified and showed potential for the non-invasive diagnosis of EC.

Nomogram for prediction of fatal outcome in patients with severe COVID-19: a multicenter study.

BACKGROUND: To develop an effective model of predicting fatal outcomes in the severe coronavirus disease 2019 (COVID-19) patients. METHODS: Between February 20, 2020 and April 4, 2020, consecutive confirmed 2541 COVID-19 patients from three designated hospitals were enrolled in this study. All patients received chest computed tomography (CT) and serological examinations at admission. Laboratory tests included routine blood tests, liver function, renal function, coagulation profile, C-reactive protein (CRP), procalcitonin (PCT), interleukin-6 (IL-6), and arterial blood gas. The SaO2 was measured using pulse oxygen saturation in room air at resting status. Independent high-risk factors associated with death were analyzed using Cox proportional hazard model. A prognostic nomogram was constructed to predict the survival of severe COVID-19 patients. RESULTS: There were 124 severe patients in the training cohort, and there were 71 and 76 severe patients in the two independent validation cohorts, respectively. Multivariate Cox analysis indicated that age ≥ 70 years (HR = 1.184, 95% CI 1.061-1.321), panting (breathing rate ≥ 30/min) (HR = 3.300, 95% CI 2.509-6.286), lymphocyte count < 1.0 × 109/L (HR = 2.283, 95% CI 1.779-3.267), and interleukin-6 (IL-6) >  10 pg/ml (HR = 3.029, 95% CI 1.567-7.116) were independent high-risk factors associated with fatal outcome. We developed the nomogram for identifying survival of severe COVID-19 patients in the training cohort (AUC = 0.900, 95% CI 0.841-0.960, sensitivity 95.5%, specificity 77.5%); in validation cohort 1 (AUC = 0.811, 95% CI 0.763-0.961, sensitivity 77.3%, specificity 73.5%); in validation cohort 2 (AUC = 0.862, 95% CI 0.698-0.924, sensitivity 92.9%, specificity 64.5%). The calibration curve for probability of death indicated a good consistence between prediction by the nomogram and the actual observation. The prognosis of severe COVID-19 patients with high levels of IL-6 receiving tocilizumab were better than that of those patients without tocilizumab both in the training and validation cohorts, but without difference (P = 0.105 for training cohort, P = 0.133 for validation cohort 1, and P = 0.210 for validation cohort 2). CONCLUSIONS: This nomogram could help clinicians to identify severe patients who have high risk of death, and to develop more appropriate treatment strategies to reduce the mortality of severe patients. Tocilizumab may improve the prognosis of severe COVID-19 patients with high levels of IL-6.

A three-microRNA panel in serum as novel biomarker for papillary thyroid carcinoma diagnosis.

BACKGROUND: Accumulating evidence has revealed that circulating microRNAs (miRNAs) can serve as non-invasive biomarkers for cancer diagnosis. This study aimed to identify differentially expressed miRNAs in serum which might become potential biomarkers for non-invasive diagnosis of papillary thyroid carcinoma (PTC). METHODS: The experiment was carried out between 2015 and 2017. In the screening stage, the Exiqon miRNA quantitative real-time polymerase chain reaction (qPCR) panel was applied to select candidate miRNAs. In the following training, testing, and external validation stages, the serum samples of 100 patients and 96 healthy controls (HCs) were analyzed to compare the expression levels of the identified miRNAs. The areas under the receiver operating characteristic curves (AUCs) were calculated to assess the diagnostic value of the identified signature. RESULTS: Three miRNAs (miR-25-3p, miR-296-5p, and miR-92a-3p) in serum were consistently up-regulated in PTC patients compared with HCs. A three-miRNA panel was constructed by logistic regression analysis and showed better diagnostic performance than a single miRNA for PTC detection. The AUCs of the panel were 0.727, 0.771, and 0.862 for the training, testing, and external validation stage, respectively. Meanwhile, the panel showed stable capability in differentiating PTC patients from patients with benign goiters, with an AUC as high as 0.969. For further exploration, the three identified miRNAs were analyzed in tissue samples (23 PTC vs. 23 HCs) and serum-derived exosomes samples (24 PTC vs. 24 HCs), and the altered expression in the tumor also indicated their close relationship with PTC disease. CONCLUSION: We identify a three-miRNA panel in serum which might serve as a promising biomarker for PTC diagnosis.

Serum microRNA expression profiling revealing potential diagnostic biomarkers for lung adenocarcinoma.

BACKGROUND: Recent studies have demonstrated that microRNAs (miRNAs) in the blood circulation can serve as promising diagnostic markers for cancers. This four-stage study aimed at finding serum miRNAs as potential biomarkers for lung adenocarcinoma (LA) diagnosis. METHODS: The study was carried out between 2016 and 2017. The Exiqon miRNA qPCR panel (3 LA vs. 1 normal control [NC] pooled serum samples) was used for initial screening to acquire miRNA profiles. Thirty-five dysregulated miRNAs were further evaluated in the training (24 LA vs. 24 NCs) and testing stages (110 LA vs. 110 NCs) using quantitative real-time polymerase chain reaction assays. RESULTS: Four serum miRNAs (miR-133a-3p, miR-584-5p, miR-10b-5p, and miR-221-3p) were significantly overexpressed in LA patients compared with NCs. The diagnostic value of the four-miRNA panel was validated by an external cohort (36 LA vs. 36 NCs). The areas under the receiver operating characteristic curve of the four-miRNA panel in the training, testing, and external validation stages were 0.734, 0.803, and 0.894 respectively. Meanwhile, the expression level of miR-221-3p was much higher in LA tumor samples than that in the adjacent normal tissues (19 LA vs. 19 NCs). The expression level of miR-10b-5p was also elevated in the serum-derived exosomes samples (18 LA vs. 18 NCs). The expression of miR-133a-3p, miR-584-5p, and miR-10b-5p was significantly elevated in LA patients with epidermal growth factor receptor mutation compared with NCs. CONCLUSION: The study established a four-miRNA signature in serum that could improve the diagnostic capability of LA.

Identification of a 7-microRNA signature in plasma as promising biomarker for nasopharyngeal carcinoma detection.

BACKGROUND: Circulating microRNAs (miRNAs) have become reliable sources of non-invasive biomarkers for cancer diagnosis. Identification of promising miRNA biomarkers in plasma might benefit a lot to the detection of nasopharyngeal carcinoma (NPC). METHODS: The Exiqon miRNA qPCR panel was used in the screening stage to identify candidate miRNAs, which were further verified by quantitative reverse transcription polymerase chain reaction (qRT-PCR) in the following three stages among plasma samples from 200 NPC patients and 189 healthy donors (as normal controls [NCs]). The identified miRNAs were further explored in tissue specimens (48 NPC vs 32 NCs) and plasma exosomes (32 NPC vs 32 NCs). Survival analyses were ultimately conducted by Cox regression models and Kaplan-Meier curves using log-rank tests. RESULTS: We identified a 7-miRNA signature including let-7b-5p, miR-140-3p, miR-144-3p, miR-17-5p, miR-20a-5p, miR-20b-5p, and miR-205-5p in plasma for NPC diagnosis after four-stage validation. The areas under the receiver operating characteristic curve (AUCs) for the signature were 0.879, 0.884, 0.921, and 0.807 for the training, testing, external validation stage, and the combined three stages, respectively. In NPC tissues, miR-144-3p, miR-17-5p, miR-20a-5p, and miR-205-5p were consistently up-regulated while let-7b-5p and miR-140-3p were significantly down-regulated compared to NCs. However, none of the seven identified miRNAs were dysregulated in plasma-derived exosomes in NPC patients. As to survival analysis, none of the seven miRNAs seemed to be associated with NPC prognosis. CONCLUSION: We identified a 7-miRNA signature in plasma as promising non-invasive biomarkers for NPC detection.

MicroRNA expression profiling analysis in serum for nasopharyngeal carcinoma diagnosis.

BACKGROUND: Circulating microRNAs have become reliable sources of non-invasive biomarkers for cancer diagnosis. miRNA expression analysis in blood circulation for the identification of novel signatures might assist the early detection of nasopharyngeal carcinoma (NPC) patients. METHODS: In the screening stage, the Exiqon miRNA qPCR panel was applied for the selection of candidate miRNAs. Serum samples taken from 208 NPC patients and 238 healthy donors (as normal controls (NCs)) were assigned to into the following three stages (training (30 NPC VS. 30 NCs), testing (138 NPC VS. 166 NCs) and external validation stage (40 NPC VS. 42 NCs)) for further confirmation of differently expressed miRNAs using qRT-PCR. The identified miRNA signatures were further explored in tissue specimens (48 NPC VS. 32 NCs) and serum-derived exosomes samples (32 NPC VS. 32 NCs). RESULTS: Five miRNAs in serum including let-7b-5p, miR-140-3p, miR-192-5p, miR-223-3p and miR-24-3p were found to be significantly up-regulated in NPC patients compared to NCs. The five identified miRNAs were further combined into one panel and the areas under the receiver operating characteristic curve (AUCs) for three independent stages were 0.910 (training), 0.916 (testing) and 0.968 (external validation), respectively. miR-192-5p and miR-24-3p were consistently up-regulated in NPC tissues while let-7b-5p and miR-140-3p were conversely down-regulated. In serum-derived exosomes samples, no expression difference was observed between NPC patients and NCs. CONCLUSION: A five-miRNA signature was identified in serum to be potential biomarkers for NPC detection.

A Panel of 12-lncRNA Signature Predicts Survival of Pancreatic Adenocarcinoma.

Background: Recent studies have highlighted the important roles of long non-coding RNAs (lncRNAs) in pancreatic adenocarcinoma (PCa) prognosis. However, most studies explored a limited number of lncRNAs based on small sample size. Methods: Systematic and comprehensive analysis of the data from The Cancer Genome Atlas (TCGA) was performed to identify a panel of lncRNA signature for predicting prognosis in PCa. Results: A total of 160 PCa patients with complete clinical data were included in our study. Twelve lncRNAs were identified to be significantly associated with overall survival (OS) in PCa patients using Cox regression analysis. A risk score formula was constructed to assess the prognostic value of the lncRNA signature in PCa. Patients with high risk score had worse OS than those with low risk score. The multivariate Cox regression analyses revealed that the lncRNA signature was an independent prognostic factor. Additionally, the signature might act as an indicator to predict treatment outcome. Functional enrichment analyses showed that the lncRNAs might involve in several molecular pathways closely related with PCa such as DNA replication, pancreatic cancer and regulation of tor signaling. Conclusions: Our study demonstrated a lncRNA signature including 12 lncRNAs with the potential to be served as an independent prognostic biomarker of PCa.

A three plasma microRNA signature for papillary thyroid carcinoma diagnosis in Chinese patients.

Whether plasma miRNAs could be used as novel non-invasive biomarkers in diagnosing papillary thyroid carcinoma (PTC) remains unknown. In this study, we designed a four-phase study to identify differentially expressed plasma miRNAs in Chinese PTC patients. Exiqon panel was initially utilized to conduct plasma miRNA profile (3 PTC pools VS. 1 healthy control (HC) pool; each 10 samples were pooled as 1 sample). The dysregulated miRNAs were then analyzed in the training (30 PTC VS. 30 HCs), testing (57 PTC VS. 54 HCs) and external validation phases (33 PTC VS. 30HCs). The identified miRNAs were further affirmed in benign nodules (2 nodular goiter (NG) pool VS. 1 HC pool). We also verified the expression of identified miRNAs in 17 matched malignant and normal tissue samples, NG plasma samples (29 PTC VS. 29 NG) and plasma exosomes (25 PTC VS. 25 HCs). Receiver operating characteristic (ROC) curves were constructed to evaluate the diagnostic value of the identified miRNAs. As a result, the screening phase demonstrated 30 dysregulated plasma miRNAs in PTC patients compared with HCs. After multiphase experiment processes, miR-346, miR-10a-5p and miR-34a-5p were found significantly elevated in PTC plasma samples relative to HCs. The areas under the ROC curve (AUC) of the three-miRNA panel for the training, testing and validation phases were 0.926, 0.811 and 0.816, separately. The panel could also differentiate PTC from NG with the AUC of 0.877. MiR-346 and miR-34a-5p but not miR-10a-5p were up-regulated in PTC tissues. And the three miRNAs showed consistently up-regulation in PTC plasma exosomes. In conclusion, our study established a three-miRNA panel in plasma with considerable clinical value in discriminating PTC from HC or NG.

A panel of seven-miRNA signature in plasma as potential biomarker for colorectal cancer diagnosis.

Colorectal cancer (CRC) has been one of the most commonly diagnosed cancers in global. The differential expression profiles of microRNAs (miRNAs) in CRC plasma of patients have the potential to serve as a diagnostic biomarker. We conducted a four-stage study to identify the potential plasma miRNAs for CRC detection. In the initial screening phase, Exiqon panel (miRCURY-Ready-to-Use-PCR-Human-panel-I + II-V1.M) including 3 CRC pools and 1 normal controls (NCs) pool were applied to acquire miRNA profiles. In the training stage (30 CRC VS. 30 NCs) and testing stage (79 CRC VS. 76 NCs), quantitative real-time polymerase chain reaction (qRT-PCR) was utilized to conduct candidate miRNA profiles. Then the identified miRNAs were verified in external validation stage (30 CRC VS. 26 NCs). Expression levels of identified miRNAs were assessed in tissue samples (24 pairs) and plasma exosomes (18 CRC VS. 18 NCs). Receiver operating characteristic (ROC) curves were constructed to evaluate the diagnostic accuracy. Seven miRNAs (miR-103a-3p, miR-127-3p, miR-151a-5p, miR-17-5p, miR-181a-5p, miR-18a-5p and miR-18b-5p) were significantly overexpressed in CRC compared with NCs. Area under the ROC curve of the seven-miRNA signature was 0.762, 0.824 and 0.895 for the training, testing and the external validation stages, respectively. Additionally, miR-103a-3p, miR-127-3p, miR-17-5p and miR-18a-5p were discovered significantly up-regulated in CRC tissues; while miR-17-5p, miR-181a-5p, miR-18a-5p and miR-18b-5p were significantly elevated in CRC plasma exosomes. In conclusion, we established a seven-miRNA signature in the peripheral plasma for CRC detection.

Five serum-based miRNAs were identified as potential diagnostic biomarkers in gastric cardia adenocarcinoma.

BACKGROUND: Circulating microRNAs (miRNAs) have been implicated as novel biomarkers for various types of cancers. The aim of the study is to identify serum miRNAs with potential in detecting gastric cardia adenocarcinoma (GCA). METHODS: A three-phase study was designed with 102 GCA patients and 84 cancer-free controls. In the screening phase (3 GCA pools vs. 1 normal control (NC) pool), a total of 35 miRNAs were identified using quantitative reverse transcription polymerase chain reaction (qRT-PCR) based Exiqon panel. Subsequently, these miRNAs were further assessed by qRT-PCR in the training phase (30 GCAs vs. 30 NCs) and testing phase (72 GCAs vs. 54 NCs). Finally, the expression levels of the identified miRNAs were assessed in GCA tissues and exosomes. RESULTS: Five up-regulated miRNAs (miR-200a-3p, miR-296-5p, miR-132-3p, miR-485-3p and miR-22-5p) were identified in serum of the GCA patients compared with NCs. The areas under the receiver operating characteristic curve (AUCs) of the five-miRNA panel were 0.766 and 0.724 for the training and testing phases, respectively. In addition, miR-200a-3p, miR-296-5p, miR-485-3p and miR-22-5p were significantly up-regulated in GCA tissues. However, none of the miRNAs in the exosomes showed different expression between GCA patients and NCs. CONCLUSIONS: We identified a five-miRNA panel in peripheral serum samples as a non-invasive biomarker in detection of GCA.

Identification of four plasma microRNAs as potential biomarkers in the diagnosis of male lung squamous cell carcinoma patients in China.

Dysregulated microRNAs (miRNAs) in the plasma of patients with lung squamous cell carcinoma (LSCC) might serve as biomarkers for LSCC diagnosis. The expression of miRNAs was performed using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) on the basis of Exiqon panels in the initial screening phase including three male LSCC pool samples and one normal control (NC) pool sample (per 10 samples were pooled as one pool sample). After the training (32 LSCC vs. 31 NCs), the testing (55 LSCC vs. 55 NCs), and the external validation (15 LSCC vs. 15 NCs) stages via qRT-PCR, a four-miRNA signature (miR-181a-5p, miR-21-5p, miR-106a-5p, and miR-93-5p) was identified for LSCC detection. Areas under the receiver operating characteristic (ROC) curve (AUC) of the four-miRNA panel for the training, the testing, and the external validation phases were 0.795, 0.827, and 0.914, respectively. Then, the four miRNAs were explored in LSCC tissue samples (23 LSCC vs. 23 NCs), and their expression was significantly up-regulated. However, none of the four miRNAs found significantly up-regulated in plasma exosomes expect miR-93-5p with borderline significance (16 LSCC vs. 16 NCs). In summary, our study established a four-miRNA peripheral plasma signature, which contributed to diagnosing male LSCC patients in China to a certain degree.

Circulating microRNAs from the miR-106a-363 cluster on chromosome X as novel diagnostic biomarkers for breast cancer.

PURPOSE: Novel noninvasive biomarkers with high sensitivity and specificity for the diagnosis of breast cancer (BC) are urgently needed in clinics. The aim of this study was to explore whether miRNAs from the miR-106a-363 cluster can be detected in the circulation of BC patients and whether these miRNAs can serve as potential diagnostic biomarkers. METHODS: The expression of 12 miRNAs from the miR-106a-363 cluster was evaluated using qRT-PCR in 400 plasma samples (from 200 BC patients and 200 healthy controls (HCs)) and 406 serum samples (from 204 BC patients and 202 HCs) via a three-phase study. The identified miRNAs were further examined in tissues (32 paired breast tissues), plasma exosomes (from 32 BC patients and 32 HCs), and serum exosomes (from 32 BC patients and 32 HCs). RESULTS: Upregulated levels of four plasma miRNAs (miR-106a-3p, miR-106a-5p, miR-20b-5p, and miR-92a-2-5p) and four serum miRNAs (miR-106a-5p, miR-19b-3p, miR-20b-5p, and miR-92a-3p) were identified and validated in BC. A plasma 4-miRNA panel and a serum 4-miRNA panel were constructed to discriminate BC patients from HCs. The areas under the receiver-operating characteristic curves of the plasma panel were 0.880, 0.902, and 0.858, and those of the serum panel were 0.910, 0.974, and 0.949 for the training, testing, and external validation phases, respectively. Two overlapping miRNAs (miR-106a-5p and miR-20b-5p) were consistently upregulated in BC tissues. Except for the expression of the plasma-derived exosomal miR-20b-5p, the expression patterns of exosomal miRNAs were concordant between plasma and serum, indicating the potential use of exosomal miRNAs as biomarkers. CONCLUSION: We identified four plasma miRNAs and four serum miRNAs from the miR-106a-363 cluster as promising novel biomarkers for the diagnosis of BC.

Plasma microRNA signature of patients with IgA nephropathy.

We looked for differentially expressed MicroRNAs (miRNAs) in Immunoglobulin A nephropathy (IgAN). Forty-eight miRNAs were identified through the initial screening phase (2 IgAN pools vs. 1 normal control (NC) pool) using quantitative reverse transcription polymerase chain reaction (qRT-PCR) based Exiqon panel (miRCURY-Ready-to-Use-PCR-Human-panel-I + II-V1.M). By qRT-PCR, these miRNAs were further assessed in the training (32 IgAN VS. 31 NCs) and testing stages (51 IgAN VS. 51 NCs). The renal pathological lesions of patients with IgAN were evaluated according to Lee's grading system. We discovered a plasma miRNA signature including four up-regulated miRNAs (miR-148a-3p, miR-150-5p, miR-20a-5p and miR-425-3p) and the areas under the receiver operating characteristic (ROC) curve (AUC) were 0.80 and 0.76 for the training and testing stage, respectively. The expression of the four miRNAs in IgAN grade I-II subgroups (according to Lee's grading system) was obviously higher than that in IgAN grade III-V (P < .05). In summary, the plasma expression of miR-148a-3p, miR-150-5p, miR-20a-5p and miR-425-3p were up-regulated in patients with IgAN, especially the early-stage disease. Further studies are needed to explore the roles of the four miRNAs in the pathogenesis and progression of IgAN.